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The implementation of neural networks (NNs) on edge devices enables local processing of wireless data, but faces challenges such as high computational complexity and memory requirements when deep neural networks (DNNs) are used. Shallow neural networks customized for specific problems are more efficient, requiring fewer resources and resulting in a lower latency solution. An additional benefit of the smaller network size is that it is suitable for real-time processing on edge devices. The main concern with shallow neural networks is their accuracy performance compared to DNNs. In this paper, we demonstrate that a customized adaptive activation function (AAF) can meet the accuracy of a DNN. We designed an efficient FPGA implementation for a customized segmented spline curve neural network (SSCNN) structure to replace the traditional fixed activation function with an AAF. We compared our SSCNN with different neural network structures such as a real-valued time-delay neural network (RVTDNN), an augmented real-valued time-delay neural network (ARVTDNN), and deep neural networks with different parameters. Our proposed SSCNN implementation uses 40% fewer hardware resources and no block RAMs compared to the DNN with similar accuracy. We experimentally validated this computationally efficient and memory-saving FPGA implementation of the SSCNN for digital predistortion of radio-frequency (RF) power amplifiers using the AMD/Xilinx RFSoC ZCU111. The implemented solution uses less than 3% of the available resources. The solution also enables an increase of the clock frequency to 221.12 MHz, allowing the transmission of wide bandwidth signals.
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Future wireless networks are planned to service many applications with an Ultra Low-Latency (ULL) requirement. Numerous 6G systems have been proposed including more traditional electro-magnetic (EM) antenna transmissions and optical wireless communications (OWC). For extremely wide-band operation, the traditional approaches require digital pre-distortion and other processing techniques which, in turn, require more computational resources and processing times thus increasing latency. Alternatively, OWC has the potential for extremely wide bandwidths in 6G without the need for as much digital signal processing. In order to realise ULL performance, a minimum number of digital signal processing (DSP) blocks is required, as well as an optimal design of each of these. In this letter, we propose a DSP solution for ULL and peak to average power ratio (PAPR) reduction for OWC systems. Unitary checkerboard precoding - orthogonal frequency division multiplexing (UCP-OFDM) is chosen as the modulation scheme and has been implemented within a single digital block avoiding the use of standard OFDM which would otherwise require multiple digital blocks. Experimentally validated results successfully demonstrate a 2.21184 GSps wireless link at distances of up to 2m in noisy daylight settings. Bit error rates (BER) of 0 at root mean square (RMS) error vector magnitude (EVM) of 4.09% are achieved. A complete digital line-up of an OWC transmitter chain for this work contains only three core blocks and ULL of less than 400 ns.
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We present a case of a 66-year-old man with a cutaneous Balamuthia mandrillaris lesion that progressed to fatal granulomatous amoebic encephalitis. We provide a summary of Australian cases and describe the clinical features and approach to diagnosing this rare but devastating condition, including the importance of PCR for diagnosis.
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Amebíase , Balamuthia mandrillaris , Encefalite Infecciosa , Humanos , Masculino , Idoso , Amebíase/diagnóstico , Encefalite Infecciosa/diagnóstico , Evolução Fatal , Biópsia , Pele/patologia , Antiprotozoários/uso terapêutico , Fluconazol/uso terapêuticoRESUMO
PURPOSE: To estimate the clinical impact of differences between delivered and planned dose using dose metrics and normal tissue complication probability (NTCP) modeling. METHODS: Forty-six consecutive patients with prostate adenocarcinoma between 2010 and 2015 treated with intensity-modulated radiation therapy (IMRT) and who had undergone computed tomography on rails imaging were included. Delivered doses to bladder and rectum were estimated using a contour-based deformable image registration method. The bladder and rectum NTCP were calculated using dose-response parameters applied to planned and delivered dose distributions. Seven urinary and gastrointestinal symptoms were prospectively collected using the validated prostate cancer symptom indices patient reported outcome (PRO) at pre-treatment, weekly treatment, and post-treatment follow-up visits. Correlations between planned and delivered doses against PRO were evaluated in this study. RESULTS: Planned mean doses to bladder and rectum were 44.9 ± 13.6 Gy and 42.8 ± 7.3 Gy, while delivered doses were 46.1 ± 13.4 Gy and 41.3 ± 8.7 Gy, respectively. D10cc for rectum was 64.1 ± 7.6 Gy for planned and 60.1 ± 9.3 Gy for delivered doses. NTCP values of treatment plan were 22.3% ± 8.4% and 12.6% ± 5.9%, while those for delivered doses were 23.2% ± 8.4% and 9.9% ± 8.3% for bladder and rectum, respectively. Seven of 25 patients with follow-up data showed urinary complications (28%) and three had rectal complications (12%). Correlations of NTCP values of planned and delivered doses with PRO follow-up data were random for bladder and moderate for rectum (0.68 and 0.67, respectively). CONCLUSION: Sensitivity of bladder to clinical variations of dose accumulation indicates that an automated solution based on a DIR that considers inter-fractional organ deformation could recommend intervention. This is intended to achieve additional rectum sparing in cases that indicate higher than expected dose accumulation early during patient treatment in order to prevent acute severity of bowel symptoms.
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Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Reto , Bexiga Urinária , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Dosagem RadioterapêuticaRESUMO
Deep inspiration breath-hold (DIBH) radiotherapy for left-sided breast cancer can reduce cardiac exposure and internal motion. We modified our in-house treatment planning system (TPS) to retrospectively analyze breath-hold motion log files to calculate the dosimetric effect of the motion during breath hold. Thirty left-sided supine DIBH breast patients treated using AlignRT were studied. Breath-hold motion was recorded three translational and three rotational displacements of the treatment surface the Real Time Deltas (RTD). The corresponding delivered dose was estimated using the beam-on portions of the RTDs. Each motion was used to calculate dose, and the final estimated dose was the equally weighted average of the multiple resultant doses. Ten of thirty patients had internal mammary nodes (IMN) purposefully included in the tangential fields, and we evaluated the percentage of IMN covered by 40 Gy. The planned and delivered heart mean dose, lungs V20 (volume of the lungs receiving > 20 Gy), percentage of IMN covered by 40 Gy, and IMN mean dose were compared. The averaged mean and standard deviation of the beam-on portions of the absolute RTDs were 0.81 ± 1.29 mm, 0.68 ± 0.85mm, 0.76 ± 0.85 mm, 0.96° ± 0.49°, 0.93° ± 0.43°, and 1.03° ± 0.50°, for vertical, longitudinal, lateral, yaw, roll, and pitch, respectively. The averaged planned and delivered mean heart dose were 99 and 101 cGy. Lungs V20 were 6.59% and 6.74%. IMN 40 Gy coverage was 83% and 77%, and mean IMN dose was 4642 and 4518 cGy. The averaged mean motion during DIBH was smaller than 1 mm and 1°, which reflects the relative reproducibility of the patient breath hold. On average, the mean heart dose and lungs V20 were reasonably close to what have been planned. IMN 40 Gy coverage might be modestly reduced for certain cases.
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Suspensão da Respiração , Planejamento da Radioterapia Assistida por Computador/métodos , Técnicas de Imagem de Sincronização Respiratória/métodos , Neoplasias Unilaterais da Mama/radioterapia , Feminino , Coração/diagnóstico por imagem , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Órgãos em Risco , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Respiração , Tomografia Computadorizada por Raios X/métodos , Neoplasias Unilaterais da Mama/patologiaRESUMO
Direct aperture optimization (DAO) has been used to produce high dosimetric quality intensity-modulated radiotherapy (IMRT) treatment plans with fast treatment delivery by directly modeling the multileaf collimator segment shapes and weights. To improve plan quality and reduce treatment time for our in-house treatment planning system, we implemented a new DAO approach without using a global objective function (GFO). An index concept is introduced as an inverse form of back-projection used in the CT multiplicative algebraic reconstruction technique (MART). The index, introduced for IMRT optimization in this work, is analogous to the multiplicand in MART. The index is defined as the ratio of the optima over the current. It is assigned to each voxel and beamlet to optimize the fluence map. The indices for beamlets and segments are used to optimize multileaf collimator (MLC) segment shapes and segment weights, respectively. Preliminary data show that without sacrificing dosimetric quality, the implementation of the DAO reduced average IMRT treatment time from 13 min to 8 min for the prostate, and from 15 min to 9 min for the head and neck using our in-house treatment planning system PlanUNC. The DAO approach has also shown promise in optimizing rotational IMRT with burst mode in a head and neck test case.
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Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Humanos , Masculino , Linguagens de Programação , Radiometria/métodos , Reprodutibilidade dos Testes , Software , Tomografia Computadorizada por Raios X/métodosRESUMO
Co-production is a collaborative way of working which emphasises the exchange of diverse forms of knowledge in an equal partnership for equal benefits. Co-produced research is a key strategic aim of the UK Research and Innovation (UKRI) Transforming UK Food Systems (TUKFS) Strategic Priorities Fund; this research programme brings together researchers, policymakers, industry and communities to create positive change in the way food is produced, accessed and consumed. However, more generally, there are diverse understandings of co-production and a lack of consensus on what 'good practice' looks like. Therefore, this study aimed to identify and map examples of co-production methods employed across the TUKFS programme. Two creative workshops (n = 15 participants), conversations with TUKFS researchers and stakeholders (n = 15), and systematic analysis of project documents were used to critically explore co-production activities within six TUKFS projects. A range of co-production activities were identified. Findings highlighted areas of 'messiness' and complexity, challenges associated with applying co-production approaches and practical solutions. Four key shared principles for co-production were identified: (1) Relationships: developing and maintaining reciprocity-based partnerships; (2) Knowledge: recognising the contribution of diverse forms of expertise; (3) Power: considering power dynamics and addressing imbalances; and (4) Inclusivity: ensuring research is accessible to all who wish to participate. Opportunities for reflection and reflexivity were considered crucial across all these areas. Findings contribute important insights towards a shared conceptual understanding of co-production for food system transformation research. This paper makes recommendations for researchers, practitioners, academic institutions and funders working in this area of research and practice.
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Abastecimento de Alimentos , Reino Unido , Humanos , Abastecimento de Alimentos/métodos , Participação dos Interessados , Indústria Alimentícia , Política Nutricional , PesquisaRESUMO
A new monotypic genus of whiteflies (Aleyrodidae), Gadigaleyrodes gen.n., is described and illustrated for G. froggatti sp.n. from New South Wales, Australia. Specimens were collected by W. W. Froggatt in 1899 on Syncarpia glomulifera, and subsequently by P. S. Gillespie on an unknown climbing plant. The genus has unusual morphological features with traits common to both Aleurodicinae and Aleyrodinae. The subfamily placement is discussed, and a key provided to discriminate this taxon from similar whitefly genera in Australia.
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Hemípteros/anatomia & histologia , Hemípteros/classificação , Animais , Hemípteros/crescimento & desenvolvimento , New South Wales , Pupa/anatomia & histologia , Pupa/classificação , Pupa/crescimento & desenvolvimentoRESUMO
Purpose: Pretreatment quality assurance (QA) of treatment plans often requires a high cognitive workload and considerable time expenditure. This study explores the use of machine learning to classify pretreatment chart check QA for a given radiation plan as difficult or less difficult, thereby alerting the physicists to increase scrutiny on difficult plans. Methods and Materials: Pretreatment QA data were collected for 973 cases between July 2018 and October 2020. The outcome variable, a degree of difficulty, was collected as a subjective rating by physicists who performed the pretreatment chart checks. Potential features were identified based on clinical relevance, contribution to plan complexity, and QA metrics. Five machine learning models were developed: support vector machine, random forest classifier, adaboost classifier, decision tree classifier, and neural network. These were incorporated into a voting classifier, where at least 2 algorithms needed to predict a case as difficult for it to be classified as such. Sensitivity analyses were conducted to evaluate feature importance. Results: The voting classifier achieved an overall accuracy of 77.4% on the test set, with 76.5% accuracy on difficult cases and 78.4% accuracy on less difficult cases. Sensitivity analysis showed features associated with plan complexity (number of fractions, dose per monitor unit, number of planning structures, and number of image sets) and clinical relevance (patient age) were sensitive across at least 3 algorithms. Conclusions: This approach can be used to equitably allocate plans to physicists rather than randomly allocate them, potentially improving pretreatment chart check effectiveness by reducing errors propagating downstream.
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The necessity of the rapid evolution of wireless communications, with continuously increasing demands for higher data rates and capacity Zheng (Big datadriven optimization for mobile networks toward 5g 30:44-51, 2016), is constantly augmenting the complexity of radio frequency (RF) transceiver architecture. A significant component in the configuration of such complex radio transceivers is the power amplifier(PA). Multiple distributed PAs are now common in proposed RF architectures. PAs exhibit non linear behaviour, causing signal distortion in transmission. Behavioural models offer a concise representation of a PAs characteristic performance which is extremely useful in simulating performance of multiple nonlinear power amplifiers. A considerable drawback with using the Recursive Least Squares (RLS) technique is that the instability of the coefficients during the training of the model. This manuscript provides a computationally efficient technique to detect the onset of instability during adaptive RLS training and subsequently to inform the decision to cease training of dynamic memory polynomial based behavioural models, to avoid the onset of instability. The proposed technique does not require modification of the RLS algorithm, merely an observation of the pre-exsisting autocorrelation function based update. This technique is experimentally validated using four different signal modulation schemes, LTE OFDM, 5G-NR, DVBS2X and WCDMA.
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Chart checking is a time intensive process with high cognitive workload for physicists. Previous studies have partially automated and standardized chart checking, but limited studies implement data-driven approaches to reduce cognitive workload for quality assurance processes. This study aims to evaluate feature selection methods to improve the interpretability and transparency of machine learning models in predicting the degree of difficulty for a pretreatment physics chart check. We compare chi-square, mutual information, feature importance thresholding, and greedy feature selection for four different classifiers. Random forest has the highest performance with SMOTE oversampling using mutual information for feature selection (accuracy 84.0%, AUC 87.0%, precision 80.0%, recall 80.0%). This study demonstrates that feature selection methods can improve model interpretability and transparency.
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Radioterapia (Especialidade) , Engenharia , Aprendizado de MáquinaRESUMO
PURPOSE: Our purpose was to assess the effect of workspace configuration on radiation therapists' (RTs) physical stressors, mental workload (WL), situational awareness (SA), and performance during routine treatment delivery tasks in a simulated environment. METHODS AND MATERIALS: Fourteen RTs were randomized to 2 workspace configurations while performing 4 simulated scenarios: current (not ergonomically optimized; n = 7) and enhanced (ergonomically optimized, n = 7). Physical stressors were objectively assessed using a rapid upper limb assessment tool. Mental WL was measured at the end of each simulated scenario subjectively using the NASA Task-Load Index and objectively throughout the scenario using eye-tracking metrics (pupil diameter and blink rate). SA was measured at the end of each simulated scenario subjectively using the situation awareness and review technique. Performance was measured objectively via assessment of time-out compliance, error detection, and procedural compliance. Analysis of variance was used to test the effect of workspace configuration on physical stressors, mental WL, SA, and performance. RESULTS: The enhanced configuration significantly reduced physical stressors (rapid upper limb assessment; P < .01) and resulted in a higher rate of time-out compliance (P = .01) compared with current workspace configuration. No significant effect on other metrics was measured. CONCLUSIONS: Our results suggest that an ergonomically designed workspace may minimize physical stressors and improve the performance of RTs.
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Conscientização , Carga de Trabalho , Humanos , Análise e Desempenho de TarefasRESUMO
Within artificial intelligence, machine learning (ML) efforts in radiation oncology have augmented the transition from generalized to personalized treatment delivery. Although their impact on quality and safety of radiation therapy has been limited, they are increasingly being used throughout radiation therapy workflows. Various data-driven approaches have been used for outcome prediction, CT simulation, clinical decision support, knowledge-based planning, adaptive radiation therapy, plan validation, machine quality assurance, and process quality assurance; however, there are many challenges that need to be addressed with the creation and usage of ML algorithms as well as the interpretation and dissemination of findings. In this review, the authors present current applications of ML in radiation oncology quality and safety initiatives, discuss challenges faced by the radiation oncology community, and suggest future directions.
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Inteligência Artificial/tendências , Aprendizado de Máquina/tendências , Melhoria de Qualidade , Radioterapia/métodos , Gestão da Segurança/métodos , Algoritmos , Previsões , Humanos , Controle de Qualidade , Radioterapia (Especialidade)/métodos , Radioterapia (Especialidade)/tendências , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
BACKGROUND AND PURPOSE: Behavioral medicine interventions that directly reduce arousal and negative emotions, such as relaxation training (RT), are conceptually different from interventions that temporarily increase negative emotions, such as written emotional disclosure (WED), but no studies have directly compared their efficacy. We compared the effects of RT and WED on people with tension or migraine headaches. METHODS: College students with either tension (n = 51) or migraine (n = 90) headaches were randomized to one of three groups: RT, WED, or a neutral writing control condition; four sessions were held over 2 weeks. Mood was measured before and after each session, and outcomes (headache frequency, severity, disability, and general physical symptoms) were assessed at baseline and at 1-month and 3-month follow-ups. RESULTS: As expected, RT led to an immediate increase in calmness, whereas WED led to an immediate increase in negative mood, for both headache samples. Intent-to-treat analyses showed that, for the tension headache sample, RT led to improved headache frequency and disability compared to both WED and the control group, but WED had no effect. For migraine headaches, RT improved pain severity relative to the control group, but WED again had no effect. CONCLUSIONS: A brief RT protocol was effective for tension headaches, but WED had no effect on health status for either tension or migraine headaches. Modifications to WED, such as targeting people with unresolved stress, providing guidance to enhance the potency of the writing, or including additional at-home writing and exposure exercises, may improve its efficacy for people with headaches and other health problems.
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Emoções , Transtornos de Enxaqueca/terapia , Terapia de Relaxamento/métodos , Estresse Psicológico/terapia , Cefaleia do Tipo Tensional/terapia , Adolescente , Feminino , Seguimentos , Humanos , Masculino , Transtornos de Enxaqueca/psicologia , Autorrevelação , Autoavaliação (Psicologia) , Índice de Gravidade de Doença , Estresse Psicológico/psicologia , Estudantes de Saúde Pública , Cefaleia do Tipo Tensional/psicologia , Resultado do Tratamento , Redação , Adulto JovemRESUMO
OBJECTIVES: We tested whether emotional skills and headache management self-efficacy (HMSE) moderated effects of written emotional disclosure (WED) compared with control writing and a different intervention, relaxation training (RT). DESIGN/METHODS: Undergraduates with migraine headaches reported emotional approach coping (EAC) and HMSE; were randomized to WED, RT, or control; and assessed on health measures at baseline and 3-month follow-up. RESULTS: Greater EAC predicted improvement following WED compared with RT and control, whereas low HMSE predicted improvement following both WED and RT, compared with control. CONCLUSIONS: Emotional skill may specifically - and low health management self-efficacy may generally - predict positive responses to WED.
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Adaptação Psicológica , Afeto , Aprendizagem , Transtornos de Enxaqueca/terapia , Narração , Relaxamento , Autorrevelação , Autoeficácia , Redação , HumanosRESUMO
BACKGROUND: To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. METHODS: Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods. RESULTS: For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3. CONCLUSIONS: Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.
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Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Transtornos Urinários/etiologia , Humanos , Masculino , Órgãos em Risco , Prostatectomia , Neoplasias da Próstata/cirurgia , Radiobiologia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Bexiga Urinária/efeitos da radiação , Transtornos Urinários/epidemiologiaRESUMO
With the growing use of low-molecular-weight heparins (LMWH) for the treatment and prevention of venous thromboembolism (VTE), it is important to provide an evidence-based comparison with unfractionated heparin (UFH) concerning rates of heparin-induced thrombocytopenia (HIT). Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical) patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.
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Identification of 10 white fish species associated with U.K. food products was achieved using PCR-RFLP of the mitochondrial cytochrome b gene. Use of lab-on-a-chip capillary electrophoresis for end-point analysis enabled accurate sizing of DNA fragments and identification of fish species at a level of 5% (w/w) in a fish admixture. One restriction enzyme, DdeI, allowed discrimination of eight species. When combined with NlaIII and HaeIII, specific profiles for all 10 species were generated. The method was applied to a range of products and subjected to an interlaboratory study carried out by five U.K. food control laboratories. One hundred percent correct identification of single species samples and six of nine admixture samples was achieved by all laboratories. The results indicated that fish species identification could be carried out using a database of PCR-RFLP profiles without the need for reference materials.
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Eletroforese Capilar/métodos , Produtos Pesqueiros/análise , Peixes/classificação , Peixes/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Animais , Sequência de Bases , Citocromos b/genética , DNA/análise , DNA/química , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
BACKGROUND: Low vessel-wall shear stress promotes atherosclerosis and restenosis. We conducted serial analysis of vessel-wall shear stress following placement of metal and sirolimus (SRL) stents to determine the relationship between shear stress and neointima. METHODS: Serial quantitative coronary angiography, intracoronary ultrasound (IVUS), and Doppler flow analysis were performed at baseline, immediately poststent, and at 30 and 90 days on 16 stents (metal, n = 8; SRL, n = 8) implanted in the coronary arteries of eight miniswine. Segmental vessel-wall shear stress (dyn/cm2) was calculated at 10 sections within the stent and normalized to the average proximal and distal reference vessel shear stress using IVUS and hyperemic average peak flow velocity. At 90 days, histological analysis was completed to determine vessel-wall morphometry on corresponding sections from each stent. RESULTS: Stent placement resulted in a similar degree of in-stent stenosis (-5% to 25%) and immediate post-in-stent shear stress. At 30 days, the IVUS neointimal cross-sectional area and percentage of area stenosis were significantly less in SRL (1.2+/-0.8 mm2; 12.7+/-8.5%) versus metal stents (2.3+/-0.4 mm2; 28.2+/-3.4%, P < .003). In-stent normalized shear stress was less for SRL (0.93+/-0.07) versus metal (1.07+/-0.08, P = .002) stents. At 90 days, the mean neointimal area was similar for the SRL (2.50+/-0.47 mm2) and metal stents (2.72+/-1.15 mm2). Linear regression documented a negative correlation between poststent shear stress and neointima for metal stents (r = .61, P < .0001). In the SRL stents, however, the post-in-stent shear stress had a positive correlation with neointima (r = .40, P = .0002). CONCLUSIONS: The placement of oversized stents causes alteration of segmental vessel-wall shear stress, which appears to be an important physiological stimulus for neointimal formation, and may influence the pharmacodynamics of SRL-eluting stent in the porcine coronary model.
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Implante de Prótese Vascular/métodos , Vasos Coronários/cirurgia , Sistemas de Liberação de Medicamentos/instrumentação , Sirolimo/uso terapêutico , Stents , Túnica Íntima/efeitos dos fármacos , Análise de Variância , Animais , Antibióticos Antineoplásicos/uso terapêutico , Velocidade do Fluxo Sanguíneo/fisiologia , Angiografia Coronária/métodos , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Modelos Animais , Estresse Mecânico , Suínos , Porco Miniatura , Fatores de Tempo , Túnica Íntima/fisiopatologia , Ultrassonografia de Intervenção/métodosRESUMO
BACKGROUND: Stent-based delivery of sirolimus (SRL) has shown reduction in neointimal hyperplasia and restenosis. The purpose of this study was to evaluate the chronic vascular response and the expression of cell cycle regulators after SRL-eluting stent implantation in a porcine coronary model. METHODS: Forty-nine pigs underwent placement of 109 oversized stents (control, n=54, SRL (140 microg/cm(2)), n=55) in the coronary arteries with histologic analysis and Western blot (PCNA, p27(kip1), CD45, MCP-1, IL-2, IL-6, TNF-beta) at 3, 30, 90 or 180 days. RESULTS: At 3 days, the mean thrombus area was similar for control (0.38+/-0.19 mm(2)) and SRL (0.29+/-0.09 mm(2)) stents. After 30 days, the mean neointimal area was significantly less for the SRL (1.40+/-0.35 mm(2)) versus the control stents (2.94+/-1.28 mm(2), p<0.001). At 90 and 180 days, the mean neointimal area was similar for the SRL (3.03+/-0.92 and 3.34+/-0.99 mm(2)) as compared with control stents (3.45+/-1.09 and 3.65+/-1.23 mm(2)). Western blot analysis demonstrated an increased expression of p27(kip1) in the vessel wall at 90 days for the SRL versus control stents (p=0.05) but with increased levels of PCNA in the SRL as compared with control stents (p=0.003). CONCLUSION: SRL-eluting stents favorably modulate neointimal formation for 30 days in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained presumably due to delayed cellular proliferation despite increased levels of the cyclin-dependent kinase p27(kip1) in the vessel wall.